title: Origin of monocytes and macrophages in a committed progenitor.
abstract: Monocytes, macrophages and dendritic cells (DCs) are developmentally related regulators of the immune system that share the monocyte-macrophage DC progenitor (MDP) as a common precursor. Unlike differentiation into DCs, the distal pathways for differentiation into monocytes and monocyte-derived macrophages are not fully elucidated. We have now demonstrated the existence of a clonogenic, monocyte- and macrophage-restricted progenitor cell derived from the MDP. This progenitor was a Ly6C(+) proliferating cell present in the bone marrow and spleen that generated the major monocyte subsets and macrophages, but not DCs or neutrophils. By in-depth quantitative proteomics, we characterized changes in the proteome during monocyte differentiation, which provided insight into the molecular principles of developing monocytes, such as their functional maturation. Thus, we found that monocytes and macrophages were renewed independently of DCs from a committed progenitor.
authors.affiliation: Immune Tolerance, Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Hettinger
authors.forename: David M
authors.initials: DM
authors.lastname: Richards
authors.forename: Jenny
authors.initials: J
authors.lastname: Hansson
authors.forename: Melanie M
authors.initials: MM
authors.lastname: Barra
authors.forename: Ann-Cathrin
authors.initials: AC
authors.lastname: Joschko
authors.forename: Jeroen
authors.initials: J
authors.lastname: Krijgsveld
authors.forename: Markus
authors.initials: M
authors.lastname: Feuerer
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002853:Chromatography, Liquid; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055017:Monocyte-Macrophage Precursor Cells / Q000166:cytology / Q000276:immunology*; D040901:Proteomics / Q000379:methods*; D013047:Specific Pathogen-Free Organisms; D021241:Spectrometry, Mass, Electrospray Ionization; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D053719:Tandem Mass Spectrometry